Pharmacological Regulation of Peroxisome Number in Glia
UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD
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Peroxisomes are sites of specialized biochemical reactions within all cells. The pharmaceutical regulation of peroxisome number has potential as medical therapy, but the mechanisms that control peroxisome number in brain cells are largely unknown. Our data suggest a novel relationship between cellular cholesterol homeostasis and peroxisome number in brain cells. Using primary cultures of rat cerebral cortical astrocytes, we have identified novel means of regulating the cellular density of peroxisomes via the liver X receptor LXR, a nuclear receptor that controls cholesterol efflux in cells. Our investigation reveals a novel means of pharmaceutically induced peroxisome proliferation in astrocytes and the possibility of new therapies for treating disorders in peroxisome biogenesis and metabolism. We have also provided a new line of evidence to suggest a relationship between cholesterol homeostasis peroxisome abundance that may have relevance to therapies for Alzheimer s disease and Neimann- Pick type C disease.
- Anatomy and Physiology